Coordination cages integrated into swelling poly(ionic liquid)s for guest encapsulation and separation

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.

1.                               ndercited to achieve this, and focuses solely on metal-organic cages, when the concept has been explored thoroughly with other hosts as well.There are many, many examples of guests binding in hosts that are larger        enclosed capsules exist that show this behavior that are not cited  Rebek, Reinhoudt, Gibb, Fujita, Mukherjee, Yoshizawa, Raymond, Nitschke.The     Reply: As noted by the reviewer, we are trying to explain in the introduction that guests larger than the portals of cages could be bound as well due to the flexibility and dynamic character of the soluble cages.This is actually a distinct advantage of assembled hosts in solution.This point does not represent the novelty of this work, whereas the novelty resides in how to maintain the flexibility and dynamic character of the cage in the solid state to have solution-level guest binding performance.We greatly appreciate the suggestion from the reviewer, and agree that such behaviour is not solely the merit of metal-organic cages.For instance, the group of Rebek has reported many examples to deal with guest binding/exchange mechanisms with assembled organic capsules (a typical review: Org.Biomol.Chem. 2 (2004)).We have thus modified the introduction with the addition of discussion on examples of all assembled capsules, including both metal-organic cages and purely organic cages.The contributions from Rebek, Reinhoudt, Gibb, Fujita, Mukherjee, Yoshizawa, Raymond, Nitschke have been cited and highlighted in the revised MS.

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Most frequently, the binding and release of guest requires rupture of multiple weak assembling forces to create a suitable opening of capsules, as these capsules usually possess large cavities with small windows.As proposed by Raymond (Fig. 1), 33,34 MOCs as receptors could allow guests that are too large to fit through the windows to enter the cavity by expansion of the windows or by rupture of a metal-ligand bond.Pioneering studies from Rebek and coworkers have also demonstrated that for the dimeric tennis balls, 35 softballs, 36 and a cylindrical capsule, 37 guest exchange occurs through openings formed by partial disruption of the hydrogen-bonding seams.[40][41][42][43][44][45][46][47] MS, Page 20: 35.Szabo, T., Hilmersson, G. & Rebek, J. Dynamics of assembly and guest exchange in the tennis ball.J. Am.Chem.Soc.120, 6193-6194 (1998).
37. Craig, S.L., Lin, S., Chen, J. & Rebek, J.An NMR study of the rates of single-molecule exchange in a cylindrical host capsule.J. Am.Chem.Soc.124, 8780-8781 (2002) Reply: We appreciate the suggestion from the reviewer and agree that our initial statement is too simplistic and is not precise.We have thus corrected the Introduction to highlight the importance of flexibility in molecular recognition in the revised MS.

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2][3][4][5] They are assembled from metal ions and organic ligands by coordination-driven self-assembly exploiting the reversibility of the metal-ligand bond.Although coordination cages are occasionally used in the solid state, 3,6 which are treated as porous crystalline materials similar to metal-organic frameworks (MOFs), 7-10 the solubility and host-guest chemistry of these discrete cages in solution are the most appealing.2][23][24][25][26] Nevertheless, the use of soluble MOCs in solution brings about the difficulty in material recovery; The host-guest chemistry of MOCs in the solid state may also be weakened or even not survive due to the limited flexibility and dynamicity, as discussed below.
Guest-binding is a complex process and usually gives rise to the most thermodynamically stable host-guest complexes.When designing new capsular hosts for specific guests, it is common to analyze the match in shape and size between them, and the 55% packing coefficient rule (i.e. the ideal filling of a host cavity by a guest bound through weak interactions) established by Rebek is useful in predicting molecular binding. 27Apart from the shape and size complementarity, the structural flexibility and dynamic character of assembled hosts play important roles and sometimes are even crucial factors in determining the performance of guest binding. 28,291][32]

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The necessity of heating to facilitate binding equilibration further indicated that mechanisms of both portal expansion and vertex dissociation (Fig. 1) may be at work on account of the high energy required. 33,34,40 The results are a little opaque  p4,         II 4L6 cage (Fig. 2A, tetramethylammonium (TMA + ) as the counterion), was selected as the metallohost.The synthetic procedures and characterization data are presented in Supplementary Section 2.1.This cage was water-               been known since 2008, and scores of papers have been published using it.To say that these authors showed its guest binding properties in water (rather than specifically mentioning the Nitschke group) is misleading.This may be a mis-phrasing, but it looks very bad as written.This also comes up again in p8               does really read this way.I would also check whether Nitschke has bound those 4 guests in his cages  he has definitely encapsulated them in other M4L6 cages of equivalent size.I can remember whether they were bound in this cage before, but it is highly likely.He has far more papers on the guest properties of this than ref 59.
Reply: We are sorry for not having noticed the misleading way we presented and we apologise for our initial phrasing.We have modified the corresponding sentences and also the caption of Figure 4 in the revised MS to highlight the significant contribution of the Nitschke group.Moreover, we have thoroughly checked the published literatures on this cage, and as noticed by the reviewer, there are 12 papers in total.We note that five of the papers have reported guest binding properties of the cage (Science 324, 1697-1699 (2009); Angew.Chem.Int.Ed. 47, 8297-8301 (2008); Chem.Commun.47,  457-459 (2011); Chem.Eur.J. 19, 3374-3382 (2013); J. Am.Chem.Soc.135, 7039-7046 (2013)), all of which have been added into the citation of the revised MS.In particular, none of these papers have described the four new guests, norbornane, norbornene, norbornadiene, and 7-oxabicycloheptane, and we are also completely sure that they have never been involved in any literatures from the Nitschke group after carefully checking.Although exploration of the four new guests for the cage is not the main focus of this work, these guests represent the largest sizes and volumes of guests included in this specific Fe II 4L6 cage reported to date.The binding of such large guests with MOC@PILs can highlight the high flexibility of the immobilized cage within the gels and thus the importance of swelling for guest binding.

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For such purpose, an anionic Fe II 4L6 cage (Fig. 2a, tetramethylammonium (TMA + ) as the counterion), which was reported and widely studied by the Nitschke group, 20,57-60 was selected as the metallohost.This cage is water-soluble and highly stable, and has shown fruitful guest binding properties in water.Following the reference, 57 the synthesis and characterization data are presented in Supplementary Section 2.1.

              
larger                 others have been known for decades, reviewed many times, and in many cases, the guests require            in 2001 was that the panels slow guest binding and enable discrete, long-lived Michaelis complexes.Rebek (not cited) published a whole series of papers on this in the late 1990s, with various mechanisms for the kinetics.More importantly, the binding properties of this cage are very, very well-known, and are                    the PIL, and the swelling, etc, is interesting, the whole discussion of molecular recognition is not representative of the literature.
Reply: We appreciate the helpful comment from the reviewer and feel sorry for not having explained clearly the novelty of this work in the original MS.We are actually not trying to demonstrate that            how to maintain flexibility and dynamic character of the cage in the solid state to have solution-level guest binding performance is difficult and unusual.Here we use the concept of swelling degree of polymers to control the flexibility and dynamic character of the integrated cages, allowing excellent solid-state guest binding properties of MOC@PIL identical to that in solution.Importantly, as mentioned by the reviewer, the groups of Rebek and Fujita have provided many evidences to demonstrate the requirement of ligand flexing for guest binding (two typical reviews respectively from Rebek and Fujita: Org.Biomol.Chem.2(2004); Chem.Commun., 509-518 (2001)).These can be supportive knowledge and excellent background, the discussion of which have been added into the revised Introduction and the revised References (please see the answer for Q1).
6.The concept of volume of guest (p10) is also misleading  cyclic guests rotate to fill the space in                  (again, Rebek published papers on this in the 2000s, not cited).
Reply: Many thanks to the reviewer for pointing this out.Although comparison of binding affinities of     guests is out of the focus of the manuscript, we fully agree with the reviewer that cyclic guests could rotate to fill the cavity space to have binding affinities close to that    guests.Indeed, for both types of guests, 1 H NMR spectra of host-guest complexes present only one set of signals for both occupied cages and included guests (Supplementary Figs.35-45), indicating the rapid rotation of guests within the cavities.We infer that the shape of guests may not significantly affect the thermodynamics (binding affinities), while the inclusion kinetics might be altered as we discussed in the revised Supporting Information (Supplementary section 4.1).
Moreover, we would feel very thankful to the reviewer if we could get some information on the specific paper the reviewer mentioned.2009)), but the fact of guest rotation is not discussed either.Nevertheless, if we combine investigations and conclusions of different papers, a comprehensive analysis may prove the statement.We also worry that we cannot carefully read all the papers and such a statement might be neglected due to our carelessness.
Supplementary Information, Page S14: All guests studied herein are significantly larger than the portal of the static Fe II 4L6 cage from single crystal data (1.7 Å diameter for CCDC 784594, see Supplementary Figure 20).In a dynamic system, the conformational motion of the cage is expected to enlarge its entrance portals thus allowing some small guests (e.g.CH2Cl2) to enter the cavity.Such a conformation motion is, however, insufficient to permit the entrance of larger guests.Based on the models, the shortest dimensions of bicyclic guests (5.455.97Å) are longer than those for monocyclic guests (3.545.27Å), while both are significantly larger than the diameter of the cage portal (1.7 Å).Moreover, it was previously shown that the volume and shape, described by their aspherici A (see Section 8), of guests can be correlated to their      A (inverse correlation). [5]As listed in Supplementary Table 1  A parameter of new bicyclic guests studied herein (norbornane derivatives) is one order of magnitude larger than monocyclic cyclohexane derivatives, which is consistent with the much slower inclusion kinetics observed for bicyclic guests.Moreover, the abov       conformational flexibility of guests.For instance, the transition between chair and boat conformations of cyclohexane or 1,4-dioxane could facilitate their insertion in the cage portals.The new bicyclic guests (norbornane derivatives) are larger and conformationally more rigid than monocyclic cyclohexane derivatives which further exacerbates the difference in expected inclusion kinetics.
Note that although the volumes of monocyclic guests are smaller than those of bicyclic guests that may affect the inclusion kinetics, monocyclic guests could rotate to fill the              7.             flexible and dynamic to present binding performances similar to the level under solution-state conditions even for larger   there is zero evidence for this presented by the authors, other than the result of Ka  not enough to ascribe mechanistic details.It could be a kinetic phenomenon with the PIL.Also,          this has effects on entry RATES, but not necessarily binding affinities, so this manner of analysis is flawed if the goal is to analyze mechanism of ingress.The authors mix rates and affinities in a very un-quantitative way.
Reply: After hearing the comment from the reviewer, we acknowledge the problem of our initial statement.We agree with the reviewer that the results of Ka should represent only the thermodynamics                 relevant to the inclusion kinetics.Following the suggestion from the reviewer, we have supplied additional experiments on binding kinetics.These results have been added into the revised MS and the revised Supplementary Information, as detailed below.The effect of swelling on binding kinetics and thermodynamics have been also separately discussed in the revised MS.

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To evaluate the influence of swelling of MOC@PILs on guest binding kinetics, we first measured the kinetic curves of the soluble cage and the immobilized cage within MOC@PIL 6 for binding three guests, benzene, cyclohexane, and norbornane (for details of the measurement, see Supplementary Section 5.2).The experiments were conducted through mixing the host, either the soluble or the immobilized cage, with guest-saturated aqueous solution, and the percentage of the occupied host was monitored by 1 H NMR spectroscopy.Results showed that for the smallest benzene, the binding kinetic curves of the soluble cage and the immobilized cage (MOC@PIL 6) almost overlapped, while binding of cyclohexane and norbornane with MOC@PIL 6 were much slower than with the soluble cage (Supplementary Fig 46).Moreover, we also monitored the concentration decrease of the free guests (initially fixed at 10 ppm) when in the presence of swollen MOC@PILs (2, 4, 6; 1.5 equiv. of the immobilized cage relative to the guest).MOC@PILs with higher swellability were found to generally present faster guest removal (Supplementary Fig 47).These results reveal the effect of swelling on guest uptake kinetics: The higher degree of swelling allows immobilized cage to be more flexible and dynamic to present faster binding kinetics, while small guests, such as benzene, that are relatively easy to enter the cavity, could be bound rapidly even using MOC@PIL 6 that has the lowest swellability.
We have also determined the apparent binding constants of MOC@PILs for the guests to investigate the effect of swelling on binding thermodynamics (for details of measurement, see Supplementary Section 5.3).As shown in Fig. 5a, when we used MOC@PIL 6 (Q = 5) that had the lowest swellability as the host, the apparent Ka for various guests were generally smaller than those with the soluble cage.Moreover, the reduction in binding affinity became increasingly significant upon increasing the size of guests.We have also measured the apparent Ka with swollen MOC@PILs 1-6 having different levels of swelling for benzene and norbornane (Supplementary Table 4).Results showed that for smaller benzene, no obvious alteration in apparent Ka with swollen MOC@PILs across all levels of swellability was observed, and the values were very close to the value with the soluble cage (Fig. 5b).In contrast, the apparent Ka for larger norbornane progressively increased upon increasing the swellability of MOC@PIL.These results demosntrate that the swellability is also able to modify the binding thermodynamics of the immobilized cages within MOC@PILs.We infer that the alteration of the binding affinity for the immobilized cage results from the distinct microenvironments: The immobilized cage was surrounded by cationic PIL chains and may become constrained compared to the free cage, while this effect is alleviated if the constraint around the cage loosens.

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Importantly, the swelling of MOC@PILs modified both the kinetics and thermodynamics of guest uptake, and higher degrees of swelling enabled the immobilized cages to bind guests similarly to the soluble cages.

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To evaluate the influence of swelling of MOC@PILs on guest binding kinetics, we monitored the ratio of [HG]/[H]0 as a function of time, where [HG] and [H]0 respectively represent the concentrations of the host-guest complex and the initial free host (i.e. total host), through 1 H NMR measurement.For the measurement of the binding kinetic curves of the soluble cage, a concentration of 1 mM cage in a 0.5 mL guest-saturated D2O solution was used and the 1 H NMR spectra were measured after periods of time.For the measurement of the binding kinetic curves of the immobilized cage, the same amount of cage within MOC@PIL 6 as for the soluble cage was calculated and used.Similarly, MOC@PIL 6 was added into a 0.5 mL guest-saturated D2O solution.After stirring for a period of time, the solid was separated through centrifugation and was washed with water three times to remove the surface-attached molecules of free guest.The release of cage species from MOC@PIL 6 into solution, including both guestMOC and empty cage, was achieved by adding an excess of NaNO3 and the corresponding 1 H NMR spectrum was recorded.Three guests, benzene, cyclohexane, and norbornane, were respectively investigated following the methods described above.Note that the binding of benzene with whichever the soluble or the immobilized cage was treated at rt, while the binding of the other two larger guests were conducted at 50 °C to facilitate the binding equilibration.Supplementary Figure 46.Binding kinetics of the soluble cage and swollen MOC@PIL 6 for benzene (a), cyclohexane (b), and norbornane (c).Binding kinetics of the swollen MOC@PIL 6 for benzene, cyclohexane, and norbornane (d).
We also monitored the concentration decrease of the free guests in the presence of swollen MOC@PILs to reveal the guest uptake kinetics.For benzene, cyclohexane, and norbornane, a concentration of 10 ppm in 20 mL water was prepared individually, and MOC@PIL 2, 4, or 6 was added into the aqueous solution for guest uptake (the molar ratio between immobilized cage and guest was 1.5 in each case).After stirring for periods of time, GC instrument equipped with a DB-WAX UI column was used to monitor the concentration of the guest in the solution.Note that the uptake of benzene with the immobilized cage was treated at rt, while the uptake of the other two larger guests were conducted at 50 °C to facilitate the binding equilibration.
8. The bindi               constants of cage-PIL are only estimates, as the authors state that not all the cage is released from the PIL.In addition, the concentration of free guests, many of which are volatile, could change upon centrifugation  this makes the accuracy of the numbers shown in S-Table 3   Reply: Although we have done our best to carefully perform the binding experiments and each experiment has been repeated at least once or twice, we acknowledge the unavoidable experimental error due to the complicated experimental procedures.We initially stated that not all the cage is                Ka in theory.As presented in Supplementary Section 5.3, based upon the following equation, the apparent Ka could be determined through the concentration of free guest [G] and the ratio of [HG]/[H]: The concentration of free guest [G] could be determined from integration of the NMR peaks relative to those of the tert-butanol internal standard directly, while the ratio of [HG]/[H] could be known by adding NO3  .Although the addition of NO3  was unable to exchange all the cage species on the polymer chains into the solution, the ratio between the released guestMOC and the released empty cage in solution, i.e.
[HG]/[H], should be the same as the initial ratio on the polymer chains.The apparent Ka determined in this way should be thus reliable in theory.However, as mentioned by the reviewer, the volatility of the guests as well as the complicated procedures for the measurement should affect the accuracy of the values.We have thus modified the numbers in these Supplementary Tables to make them more accurate and less ambiguous by reducing the significant figures.Moreover, the information on the repeat of experiments to calculate experimental error has been also added into the revised caption of Fig. 5.

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Fig. 5 l Guest binding affinities of MOC@PILs.(a) Normalized Ka of the Fe II 4L6 cage and the apparent Ka of MOC@PIL 6 for a series of guests with differing sizes in water.(b) Apparent Ka of MOC@PILs 1-6 for benzene and norbornane in water.The dashed green and blue lines represent the binding constants of the soluble cage for benzene and norbornane, respectively.Error ranges were calculated from triplicate experiments.

Referee: 2
In this article, the authors report the preparation and application of a hybrid material constructed from a poly(ionic liquid) (PIL) and a known negatively charged metal-organic cage (MOC).Different loadings of MOC to PIL were explored, and the materials and swelling were characterized using a number of techniques.The applications of the hybrid material in micropollutant removal from water were explored; additionally, the authors have reported novel host-guest chemistry for this MOC and used this information to extend the scope of the micropollutant removal studies.
I think this is a very clever approach to the construction of complex materials based on simple underlying principles.For me it is a clear step forward from existing work and is thus novel enough for publication in Nat.Comm.However, certain areas of discussion in this require further consideration before publication is recommended.
Reply: We appreciate the positive comments from the reviewer as well as the very helpful suggestions in the report.We have carefully addressed all the issues raised by the reviewer, as detailed below, and are very looking forward to hearing the opinion from the reviewer again.
1.The discussion in the introduction focusses on the applications of MOCs in the solution and solidstate, but some attention should be given to existing examples that bridge this gap to provide fuller context/precedent for this work.The incorporation of MOCs into polymer hydrogels is certainly relevant here, and although several references have been included to highly relevant manuscripts in this area, I think the introduction must explicitly describe this precedent.I think that the incorporation of MOCs into porous liquids is also very relevant.A recent manuscript describing permanently porous ionic liquid gels based on metal-organic polyhedra (DOI: 10.1021/jacs.3c03778)should be acknowledged.
Reply: We agree with the reviewer that the incorporation of MOCs into gels is highly relevant to the work, and this part of knowledge should be documented in the Introduction.Following the suggestion from the reviewer, we have added discussion on MOC-integrated gels, including the current advances and common challenges in this area, into the revised Introduction of the MS.Relevant references, including the recent paper describing permanently porous ionic liquid gels, have been also cited and highlighted in the revised MS.

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The unique positioning of gel materials at the boundary between liquids and solids offers attractive features when combining with MOCs. 48Particular attention has been devoted to the coupling of polymers with MOCs to prepare MOC-branched (star) or crosslinked networks. 49,502][53][54] It is envisioned that the confined solvent within the gel could provide ideal microenvironments for the coordination cages to dynamically move and flex, enabling these cages to bind guests efficiently.Similarly to hard solids, capsule-containing soft solids can also be recycled in a heterogeneous fashion.However, to our knowledge, the host-guest chemistry of these integrated MOCs is rarely explored. 51Moreover, the strategy to prepare MOCintegrated gels is currently limited to the use of MOCs as junctions.
MS, Page 21: 2. The authors state they used ICP-AES to determine the amount of the MOC immobilized in the PIL after digestion with nitric acid.I believe that this assay can detect the amount of Fe immobilized in each sample, not the amount of in-tact MOC (which is a difficult question to address).This quantification does not account for the possibility that some of the cage within the PIL could have decomposed before the digestion step.
The next experiment, in which the cage is released from the PIL after ion exchange and analysed by 1 H NMR goes some way to addressing this          would not be able to detect any non-coordinated Fe present.We still do not know what the loading of in-tact cage in each sample is.Later experiments (FTIR, 13 C MAS NMR and TGA) show increased loadings in the different samples but cannot give an absolute loading.
Reply: We appreciate the very good comment from the reviewer, which is also a difficult but important issue to address.Regarding the hypothetical presence of non-coordinated Fe II in the MOC@PILs samples, it would be unfavorable for cationic Fe II to be integrated into a cationic PIL whereas the Fe II 4L6 cage is anionic and interacts favorably with the cationic PIL.The Fe II content detected by ICP-AES thus most likely originates from the cage, or at worst, from Fe-coordinated complexes.After in-depth consideration, we have designed and conducted two sets of new experiments to test the stability of the MOC.These include the stability of the MOC when in the presence of a large excess of PIL monomers and the state of the solution cage after immobilized by PIL-NO3  .As detailed below, the results of the experiments demonstrate the high stability of the cage -no decomposition species have been observed in either case.This guarantees that the amount of the detected Fe by ICP-AES exclusively comes from the intact immobilized MOCs.These experiments as well as the corresponding discussion have been added into the revised MS and the revised Supplementary Information.

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Through simple stirring of the synthesized PIL with the Fe II 4L6 cage in water, ion exchange took place, resulting in obvious color change of the material from colorlessness to purple (Fig. 2a).The precipitate was obtained by centrifugation and was washed with pure water repeatedly until no color resulting from the free Fe II 4L6 cage was observed in the supernatant.The addition of a large amount of acetone enabled the cage-gel composite to agglomerate.The amount of the Fe II 4L6 cage in the composite could be quantified by ICP-AES for the measurement of Fe after digesting the sample with nitric acid.We infer the amount of the detected Fe to be exclusively from the intact immobilized MOCs due to the high stability of the Fe 1.The authors attributed the change of cage@PILs swelling capacity to be the outcome of (a) cage hydrophobicity and (b) the limited motion of PIL chains due to their electrostatic interaction with cages.As far as I understand, the cages with four negative charges can serve as crosslinkers to more densely link the PIL chains to prevent their swelling in water.However, the authors did not demonstrate any experiments to support this hypothesis.For instance, the authors could have demonstrated the mesoscale characterization of composites after freeze-drying.However, the only cage@PIL 4 was characterized by SEM.The authors should check all the mesoscale structures with different cage loading and discuss how the resulting morphology, size, and width would be affected by the loading amount.The authors should show evidence to support their hypothesis.
Reply: We appreciate the great suggestion from the reviewer and fully agree with the reviewer that cages with four negative charges can serve as crosslinkers to more densely link the PIL chains to prevent their swelling in water.This explanation has been added into the revised MS along with the addition of experimental evidences.Following the suggestion from the reviewer, apart from MOC@PIL 4, we have also conducted measurements of Cryo-SEM of swollen MOC@PILs 2 and 6 after freeze-drying for comparison.Results demonstrated a significant effect of cage loading on the morphology and pore size of swollen MOC@PILs.The figures and the corresponding discussion have been added into the revised MS.

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We infer this phenomenon to have two main causes: 1) the anionic cages are more hydrophobic than nitrate anions, which reduces the affinity of the composite with water; 2) each cage with four negative charges requires to be surrounded by four imidazolium cations Reply: We agree with the reviewer that quantitative analysis of the stiffness of the swollen MOC@PILs gels are very important.Following the suggestion from the reviewer, rheology studies of the gels have been conducted.Results showed that the gradual increase of the cage loading (> 0.32 g/g) within MOC@PILs led to the concomitant increase of the storage moduli, suggesting the increased stiffness.The detailed results, figures, and the corresponding discussion have been added into the revised MS and the revised Supplementary Information.
MS, Page 9: The decrease of swelling capacity and enhancement of gel stiffness with increasing MOC loadings were confirmed through rheological studies.Frequency sweep tests at 0.1% shear strain showed the storage moduli (G') dominated over the loss moduli (G'') for all the swollen gels within the tested range, indicating strong elastic response from all the samples (Fig. 3b and Supplementary Fig. 16).The G' value of hydrogel 1 was 103 Pa at an oscillatory frequency of 10.05 rad s -1 , close to the value of the parent PIL-NO3  (G' = 89 Pa) (Fig. 3a).In contrast, the gradual increase of the cage loading (> 0.32 g/g) within MOC@PILs witnessed concomitant increase of G', suggesting the increased stiffness.A G' of 1.01×10 6 Pa was obtained for MOC@PIL 6 with a maximum cage loading of 0.74 g/g, corresponding to a 10 4 -fold increase with respect to the parent PIL-NO3  .These rheology results agree with the tests of swelling capicity discussed above, revealling the role of crosslinker played by the immobilized cages. 54Moreover, time-dependent oscillatory tests demonstrated high stability of all these swollen gels (Supplementary Fig. 17).
MS, Page 8: We have proposed for the first time the potential of using swelling of polymers to control the flexibility, dynamicity, and even guest binding mechanisms of coordination cages.This concept was demonstrated by integration of anionic cages into swellable cationic PILs through ion exchange, resulting in a series of MOC@PILs having differing cage loadings.The amount of the immobilized cage within MOC@PILs were found to control the swelling ability and mechanical properties of MOC@PILs.In comparison to the conventional modulation of MOC junctions to tune the mechanical properties of MOCs-branched or crosslinked gels, 48,49  Reply: As suggested by the reviewer, we should separately consider the macroscopic swelling behavior from the microscopic crosslinking between PILs and cages, and it is very important to know the electrostatic interactions between PILs and cages.As answered for Q1 and Q2, we have supplied experiments of SEM and rheology studies to investigate the cage effect on macroscopic swelling behavior.Following the suggestion from the reviewer, we have also conducted 1 H NMR experiments to demonstrate the existence of electrostatic interactions between PILs and cages, as detailed below.MOC@PIL 1 MOC@PIL 2 MOC@PIL 2 MOC@PIL 3 MOC@PIL 3 MOC@PIL 4 MOC@PIL 4 MOC@PIL 5 MOC@PIL 5 MOC@PIL 6 MOC@PIL 6 MOC@PIL 1 MOC@PIL 2 cage@PIL MOC@PIL 3 MOC@PIL 3 MOC@PIL 4 MOC@PIL 4 MOC@PIL 5 MOC@PIL 5 MOC@PIL 6 MOC@PIL 6 G', G'' (Pa) time (s) The Fe contents of MOC@PILs were measured by ICP-AES after digesting the samples of MOC@PILs (40 mg) with concentrated nitric acid (2 mL) at 120 °C for 12 h.The amounts of the anionic cage within the eight samples of MOC@PILs were calculated to be 0.11, 0.24, 0.32 (MOC@PIL 1), 0.42 (MOC@PIL 2), 0.51 (MOC@PIL 3), 0.62 (MOC@PIL 4), 0.65 (MOC@PIL 5), and 0.74 (MOC@PIL 6) g/g, respectively, based on the amounts of Fe measured in each sample.
5. The authors did not describe why cage@PIL 6 was chosen as the representative adsorbent for the micropollutant removal and purification.This sample possesses the lowest swelling capacity and can be easily recycled from the solution without the deswelling process.As far as I understand, the addition of acetone here is to help the release of the encapsulated organic molecules rather than the deswelling.To study the effect of sample swelling behavior, the authors should compare the pollutant extraction performance among cage@PILs with different cage loading amounts.
Reply: Following the suggestion from the reviewer, we have added the reasons why we chose MOC@PIL 6 as the representative adsorbent in the revised MS.MOC@PIL 6 was chosen as the adsorbent due the high cage loading and appropriate stiffness after swelling, which could be easily recycled after adsorption.The low swellability of 6 (Q = 5) also adsorbed only a small amount of water for in-situ swelling, allowing a large proportion of water sample to be left.As suggested by the reviewer, we have also studied the effect of swelling of samples with different cage loadings on the adsorption kinetics and adsorption performance, results showed that all three samples of MOC@PILs 2, 4, 6 could achieve the complete removal of benzene, cyclohexane, and norbornane within a reasonable peroid of time.This new result, which has been added into the revised MS, constituted another important reason of using 6 as the represented adsorbent.

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Pollutant treatment is critical in modern society and adsorption is a leading technology for removing pollutants from water. 62,63The above results suggested the great potential of using swollen MOC@PILs as efficient and regenerable adsorbents for water purification.
In this context, we chose MOC@PIL 6 as the adsorbent due to the high cage loading and appropriate stiffness after swelling, which could be easily recycled after adsorption through centrifugation or filtration.The low swellability of 6 (Q = 5) also consumed only a tiny amount of water for in-situ swelling, allowing a large proportion of water sample to be left.Moreover, the above adsorption kinetic experiments of 6 (Supplementary Fig 47) also indicated the capability of complete removal of benzene, cyclohexane, and norbornane within a reasonable peroid of time.

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Moreover, we also monitored the concentration decrease of the free guests (initially fixed at 10 ppm) when in the presence of swollen MOC@PILs (2, 4, 6; 1.5 equiv. of the immobilized cage relative to the guest).MOC@PILs with higher swellability were found to generally present faster guest removal (Supplementary Fig 47).These results reveal the effect of swelling on guest uptake kinetics: The higher degree of swelling allows immobilized cage to be more flexible and dynamic to present faster binding kinetics, while small guests, such as benzene, that are relatively easy to enter the cavity, could be bound rapidly even using MOC@PIL 6 that has the lowest swellability.

Fig. 4 l
Fig.4l Host-guest chemistry of MOC@PILs.(a) Guests investigated in this work, including those that were previously reported by the Nitschke group[57][58][59][60] and the four new bicyclic guests.(b) Schematic illustration of the strategy for investigation of the host-guest chemistry of MOC@PILs.
Reversible formation of assembled hosts from subunits in solution, on the other hand, allows capsules to open dynamically to accommodate guests facilely.
J. 4,  1016-1022 (1998)), binding constants of both mono-and bicyclic guests are determined, which are shown similar, but the reason of rotation of guests within the cavity is not mentioned.Some other papers are focused on the motion and dynamics of mono/bicyclic guests (J.Am.Chem.Soc.119,11701-11702(1997);Org.Lett.10,5397-5400(2008);Eur.J. Org.Chem 2722-2728 (2007)), but binding constants are not compared one another.There is a very nice review from Rebek talking about molecular behavior in confined spaces (Acc.Chem.Res.42, 1660-1668 ( very weak.Certainly they should not be stated to 3 sig figs, and should only be described as estimates.The chart in the text (Fig 5) is probably ok, as all the affinities are relative and any errors should be                the S-Tableaffinitiesfor cage:PIL should be far more tentative in their descriptions, and not promise accuracy that is impossible.
The apparent binding constant could not be determined due to the difficulty in the assignment of peaks of the encapsulated guest on the 1 H NMR spectrum.b Due to the complicated procedures of the measurement, data are presented with only two significant figures to avoid inaccuracies.All errors are below 10%.
. Binding constants (Ka) of the soluble cage and apparent binding constants (apparent Ka) of the immobilized cage within MOC@PIL 6 for various guests in D2O.